Pancreatic cancer is a highly malignant tumor characterized by insidious onset and rapid progression. Patients with pancreatic cancer do not respond well to traditional treatments. Immune checkpoint inhibitors (ICIs) have therapeutic efficacy in non-small cell lung cancer, melanoma, and other malignant tumors. However, ICIs have limited effect on patients with pancreatic cancer, which may be related to the unique tumor microenvironment. Targeting specific sites in the microenvironment of pancreatic cancer to promote the transformation of the tumor microenvironment from an immunosuppressive state to an immune activation state may be an effective strategy to enhance the therapeutic effect of ICIs. Thus, combining ICIs with targeted therapy may be a promising strategy for pancreatic cancer treatment. In this paper, wesummarize the relative mechanisms of drugs targeting the microenvironment of pancreatic cancer and strategies combined with ICI. The aim was to provide an effective reference for combined immunotherapy to treat pancreatic cancer.